The in vitro manipulation, study and processing of individual cells continues to be of importance both for theoretical evaluation as well as for the in vitro assaying of compounds for biological activity in such cells. However, conventional biological assay systems such as flow cytometry and cell perfusion chambers are typically operated with from 1 ml to 100 ml of reagents or more. A further disadvantage of techniques involving large volumes of cells is the inability to observe the effects on a cell before, during and after it comes into contact with a candidate compound. Finally, statistical variations within a population of cells can limit the ability to resolve the effect of a compound.    Recently small disposable devices have been developed for handling biological samples and for conducting in vitro experiments on a controlled basis. For example, microchips have been used to electrophoretically separate mixtures of amino acids (1). Fluri et al. (2) also describe an integrated capillary electrophoresis device where electrophoresis is used to separate mixtures of amino acids.
The manipulation of a single cell by its electrophoretic mobility has been shown in a capillary (3). Microchips have been designed to evaluate sperm function, principally motility, for in vitro fertilization (4).
Analysis of the effects of candidate compounds on cell function demands careful handling of candidate compounds which are often limited in both quantity and concentration. The ability to observe the effect of the candidate compounds on individual cells in a device potentially suitable for a high level of multiplexing makes miniaturized analysis very attractive. Furthermore, the ability to observe the effect of a candidate compound on non-adherent cells would be beneficial.
Microfluidic systems embodied in a microchip would use small volumes, providing cost saving advantages for work involving expensive reagents, especially candidate compounds made for new drug screening and of course would reduce the amount of candidate compound required.
The ability to sort cell responses into classes and analyze each class separately would reduce the apparent statistical variation seen when large number of cells are evaluated en masse. Single cell studies would also allow the progression of events within a single cell to be evaluated, in contrast to flow cytometry where a progression of events is studied over an ensemble of cells. Statistical variations within an ensemble can limit the ability to resolve a particular effect, whereas working with individual cells will maximize resolution and signal to noise for a given event.
It would be therefore advantageous to manipulate and transport cells within a microfabricated reaction device thereby allowing the observation of the cell reactions.